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Immunohistochemical study of phosphorylated neurofilaments during the evolution of organophosphorus ester-induced
B S Jortner1, S K Perkins, M Ehrich
1Laboratory for Neurotoxicity Studies, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Tech, Blacksburg 24061-0442, USA. bjortner@vt.edu
Abstract:
Organophosphorus ester-induced delayed neuropathy (OPIDN) is manifest by delayed degeneration of distal levels of long myelinated fibers following an appropriate neurotoxic exposure. We investigated the dynamics of cytoskeletal changes during nerve fiber degeneration in this condition, focusing on the immunohistochemistry of axonal phosphorylated neurofilaments. OPIDN was produced in 5-month-old White Leghorn hens using a single 2.5 mg/kg intramuscular dose of phenyl saligenin phosphate. Hens were sacrificed on days 4, 7, 9, 15, and 20, and the tibial nerve branch to the gastrocnemius muscle was studied by light microscopy and immunohistochemistry (using the SMI 31 monoclonal primary antibody to phosphorylated neurofilaments). At post-dosing days 9, 15, and 20 various stages of OPIDN lesions were noted, including axonal swelling and myelinated nerve fiber degeneration. These were associated with intra-axonal cytoskeletal lysis, manifest by loss of immunolabeled phosphorylated neurofilaments, a process consistent with proteolysis. Aggregations of excess axonal phosphorylated neurofilaments were not observed.
Insights
Organophosphorus ester-induced delayed neuropathy (OPIDN) involves nerve fiber degeneration. This study reveals cytoskeletal breakdown and loss of phosphorylated neurofilaments during OPIDN progression in hens.
Area of Science:
- Neuroscience
- Toxicology
- Cell Biology
Background:
- Organophosphorus ester-induced delayed neuropathy (OPIDN) is a neurodegenerative condition affecting long myelinated nerve fibers.
- The precise molecular mechanisms driving nerve fiber degeneration in OPIDN remain incompletely understood.
Purpose of the Study:
- To investigate the dynamic changes in the axonal cytoskeleton during OPIDN.
- To specifically examine the role and localization of phosphorylated neurofilaments in nerve fiber degeneration.
Main Methods:
- OPIDN was induced in White Leghorn hens using phenyl saligenin phosphate.
- Tibial nerve samples were collected at various time points post-exposure (days 4, 7, 9, 15, 20).
- Light microscopy and immunohistochemistry using the SMI 31 antibody (targeting phosphorylated neurofilaments) were employed.
Main Results:
- OPIDN lesions, including axonal swelling and nerve fiber degeneration, were observed from day 9 onwards.
- These pathological changes correlated with intra-axonal cytoskeletal lysis.
- A significant loss of immunolabeled phosphorylated neurofilaments was evident, suggesting proteolysis.
Conclusions:
- The study demonstrates that cytoskeletal lysis, characterized by the loss of phosphorylated neurofilaments, is a key feature of OPIDN.
- Proteolysis of phosphorylated neurofilaments contributes to nerve fiber degeneration in OPIDN.
- No aggregation of excess phosphorylated neurofilaments was detected during the observed stages of OPIDN.